Mark starred on Cubs teams that included Ryne Sandberg, Andre Dawson and Sammy Sosa, and despite not being a power-hitter, he was a consistent, steady hitter, compiling almost 2,500 hits and more than 500 doubles during his 16-year career and for a few years batted clean-up for the Cubs. He had a career on-base percentage of .383 and collected four Gold Glove Awards and was a three-time all star (1993, 1995, 1997).

Mark helped lead the Cubs to the N.L Eastern Division title in 1989 and the N.L. Wild Card in 1998. In the 1989 N.L.C.S., Grace emerged as a star as he was perhaps the top performer of the series. Although the Cubs lost to the Giants, he batted an amazing .647 in the five game contest with a home run and three doubles, while driving in 8 of the total 16 runs scored by the Cubs in the series.

Grace led the team in average (.325), OBP (.393), hits (193), walks (71), doubles (39), and RBI (98 - a career high) in 1993 and was selected as an alternate to the National League All Star Team for the first time in his career. He also hit for the cycle on May 9 that year, and as of 2013 is the last Cub to have done so.[2] 1995 would prove to be his best year, as Mark hit .326 with a .395 OBP and a .516 SLG, and hit 51 doubles (which led the National League). He was once again named to the National League All-Star team. Grace holds the distinction of collecting the most hits (1,754) in the decade of the 1990s. Grace and Pete Rose are the only major league baseball players to lead a decade in hits and not be in the Baseball Hall of Fame. Grace also had the most doubles in the 1990s with 364 and the most sacrifice flies with 73.

The song that played most frequently on the Wrigley Fieldorgan prior to a Grace at bat was "Taking Care of Business" which Grace explained was due to his bit part in a Jim Belushi film of the same name.

Mark Grace signed with the Arizona Diamondbacks on December 8, 2000 with a $6 million, two-year contract after the Cubs declined to offer salary arbitration. The deal included a mutual $3 million option year in 2003. He received $5.3 million in his last season with the Cubs but accepted less money for the opportunity to live year-round at his home in suburban Scottsdale, Arizona with his family. "For me to remain a Cub, the Cubs would have wanted to want me back and the Cubs would have had to win," Grace said at the time. "Neither of those happened and I'm one proud Diamondback now."[3]

Grace wore his familiar No. 17 in Arizona where he played for three more seasons, including helping the Diamondbacks win the 2001 World Series. He never before even visited Yankee Stadium, and belted a home run in Game 4 of the series.[4] Grace was also responsible for leading off the bottom of the 9th inning with a single off Yankee pitcher Mariano Rivera which rallied the Arizona Diamondbacks to an improbable come-from-behind victory in Game 7. His .515 batting average in League Championship Series play is a record for players in at least 10 games.

During a 19–1 defeat to the Los Angeles Dodgers in 2002, Grace pitched an inning of relief. He surrendered one run on catcherDavid Ross's first career home run. Grace also impersonated teammate Mike Fetters, who from the stretch takes a deep breath, then quickly turns his head towards the catcher.

On September 26, 2003, Grace announced his retirement from baseball. He continued his involvement in the game as a television color commentator for the Diamondbacks and for Fox Saturday Baseball. Grace's trademark unusual style and off-the-wall terms (such as "slumpbuster", "never-say-die-mondbacks", and "Gas!") bring a unique quality to the Diamondbacks' broadcast team. Grace has stated a desire to coach a major league team in the future. He was considered for the Diamondbacks' managerial position following the 2004 season, but the Diamondbacks hired Bob Melvin instead.

Grace also agreed to a deal with Fox Sports in 2007. He originally rotated between the studio and the no.3 booth. He was then promoted to the no.2 booth with Thom Brennaman for the 2008 and 2009 season, and Dick Stockton for the 2010 season. He reunited with Brennaman in 2011 before leaving the network at the end of the regular season. He was replaced by Eric Karros who had worked on the no.3 team with Kenny Albert.

On August 24, 2012 Grace requested an indefinite leave of absence from the booth, and at the end of the 2012 season, the team announced that he would not be returning for the 2013 season.[6]

His ex-wife, Michelle, was also married to Ray Liotta, who played baseball player "Shoeless" Joe Jackson in Field of Dreams. As of 2006, he is divorced from his second wife Tanya, who stars on the VH1 show Baseball Wives.

On October 3, 2012 a grand jury in Arizona indicted Grace on four felony counts stemming from his August 23, 2012 arrest in Scottsdale on suspicion of driving under the influence, driving with a suspended license and without an interlock device.[9] The Diamondbacks announced the following day that Grace would not return to his television broadcasting duties with the club. He subsequently pleaded guilty and was sentenced to four months in jail on January 31, 2013. The sentence included work-release jail time as well as two years of supervised probation. An interlock device was required to be installed in his vehicle for six months.[10]

Grace became eligible for the National Baseball Hall of Fame in 2009; 75% of the vote was necessary for induction, and 5% was necessary to stay on the ballot. Grace received 4.1% of the vote and was dropped off the ballot.

"For 16 seasons, Mark Grace brought enthusiasm, humor and amazing talent to the game of baseball. As a Chicago Cub, Mark led his team on the field and in the hearts of its fans from his rookie season in 1988 through the end of the 2000 season. His thirteen seasons playing for the Cubs established him as one of the game's "good guys" with a throwback style of getting his uniform dirty and having fun on and off the field."[11]